Synthetic Tissues build themselves

June 6, 2018

Tissues will be able to repair themselves on their own following a recent development.

It has been a long-lasting mystery that how a single fertilized egg transforms into different organs like eyes and brain. A recent research did help the scientists to untangle this a bit as a half-human half-chicken embryo was created in a laboratory in the United States. Scientists are hopeful that the answer to this fundamental query of developmental biology will also enable them to regrow organs by healing the damaged tissues.

In a recent study, researchers demonstrated that groups of cells can be instructed to organize themselves in a multi-layered structure. This concept is similar to what we have in first stages of embryonic development and simple organisms. Wendell Lim, one of the Senior Authors of the study who is the Chair and Byers Distinguished Professor in the Cellular and Molecular Pharmacology Department at UCSF, described the natural systems of biology in the following words:

“What is amazing about biology is that DNA allows all the instructions required to build an elephant to be packed within a tiny embryo. DNA encodes an algorithm for growing the organism — a series of instructions that unfolds in time in a way we still don’t really understand. It’s easy to get overwhelmed by the complexity of natural systems, so here we set out to understand the minimal set of rules for programming cells to self-assemble into multicellular structures.”

Cells communicate mutually during the formation of biological structures to make collective decisions about the pattern of their organization. This decision is then coordinated to all of them to ensure proper functioning. The team of researchers that performed this latest research used synNotch, a powerfully customizable synthetic signaling molecule, to replicate that procedure. It was developed recently in Lim’s lab and Satoshi Toda, a Postdoctoral Researcher at UCSF who led the research, decided to utilize this for their study. It helped them to program cells that responded to specific cell-to-cell communication signals with bespoke genetic programs.

During this study, an experiment was performed in which two groups of cells were programmed to organize them into a two-layered spherical structure. A group of blue cells was to express a signaling protein on their surface while a group of colorless cells was equipped with custom synNotch receptors which were supposed to detect the protein signals from the blue cells. No growth in their populations was observed when both these groups were kept away from each other.

However, remarkable results were observed once they were mixed. The protein from the blue cells triggered the synNotch receptors on the clear ones and they produced a green marker protein called GFP alongside sticky cadherin. Consequently, clear cells turned green and clustered together to form a central core which was surrounded by a layer of their blue partners.

As the results of these simple experiments were promising, researchers tried some complex ways of self-assembling the groups of cells. They started with a single group of cells that divided themselves into two distinct teams before forming a layered structure. Similarly, three-layered spheres were also tried. The cells that formed the beginnings of ‘Polarity’, the distinct axes of head-toe, front-back, and left-right, were also produced during this research.

This kind of cells plays an instrumental role in defining the body plans of different multicellular organisms. Different types of cadherin adhesion molecules guide cellular groups to either divide into four distinct radial arms or to form head and tail sections. These experiments revealed that simpler cells can be programmed to form complex structures. This phenomenon can be related to a single fertilized egg which divides itself to form different parts of the body.

The researchers also tested the self-repairing capabilities of these complex structures during this study. The two co-authors, Sindy Tang and Lucas R. Blauch of Stanford University, developed a micro-guillotine which was used to cut the multi-layered spheres in half. It was observed that the remaining cells reorganized themselves pretty rapidly according to their intrinsic program. Lim plans to develop even more complex cellular structures in the future by introducing multiple layers of synNotch signaling.

This means that there will be a cascading operation where the initiation of one synNotch receptor will trigger the cells to produce more distinct synNotch receptors. He believes that this will ultimately lead to elaborate structures which are needed for growing tissues for repairs and transplants.

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